Immune-mediated diseases such as type 1 diabetes (T1D), multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosis are reaching epidemic proportions in the US. T1D affects an estimated 1.25 million Americans, with more than 30,000 new patients diagnosed annually, resulting in an estimated $15 billion in health care costs in the US by 2024. T1D is an autoimmune disease characterized by effector T-cell mediated destruction of insulin-producing ?-cells, which renders the patient unable to produce insulin and forces the patient to constantly monitor their glucose levels and manually administer insulin for the remainder of their life. Ultimately, glucose metabolism is interrupted, resulting in the development of life-threatening complications such as heart disease and renal failure. Clearly, the cost associated with treatment and care of T1D in the US is significant, both to society and the individual, and a novel therapy is desperately needed to thwart this aberrant autoimmune activity. This is a need that OneVax is committed to fulfilling. The biomedical research community has sought better ways to induce specific immune tolerance for nearly 50 years. Clinical intervention trials using immunomodulatory agents (e.g., anti-CD3) have failed to meet clinical endpoints, despite positive results in phase I/II trials. Moreover, traditional vaccine strategies providing auto-antigen or peptides alone failed to adequately block ongoing beta cell immunity. Thus, a new treatment strategy that is both potent and durable is required to effectively halt the ongoing attack in T1D. Therapeutic vaccination approaches for T1D utilizing dendritic cells (DCs) hold promise to correct antigen- specific autoimmune responses, but current strategies involving exogenous manipulation of DCs are unstable, inefficient and expensive. OneVax has developed a novel in vivo tolerogenic vaccine using GMP-compatible components (designated OV-01) to administer immuno-modulatory factors to phagocytic DCs, the most efficient antigen presenting cell type of the body and key regulator of the immune system. OV-01 is minimally invasive, requires no costly cell isolation and storage, and, due to its stable composition, has an extended shelf- life, simplifying manufacturing and shipping. Preliminary data strongly suggests that this biomaterial-based, microparticle vaccine system holds great promise for correcting autoimmune responses in T1D. The overwhelmingly positive and extensive data collected thus far merits the submission of this Direct-to-Phase II SBIR proposal wherein OneVax will establish scalability and stability parameters for OV-01, determine the minimum effective dose in preventing diabetic onset, determine its capacity for reversing established diabetes, and satisfy the FDA mandated pre-clinical safety assessment. Most importantly, strategic collaborations between OneVax and the Sid Martin Biotechnology Incubator, the Biomedical Engineering Department, the College of Medicine, and the Diabetes Institute at the University of Florida boost the capability of OneVax to complete the desired goals and to bring a much-needed therapy for T1D closer to the clinic.